Stem cell factor (SCF), the principal growth factor for human mast cells, is also a known chemotactic factor for these cells. As it is known that Kit, the receptor for SCF, has been shown to exhibit activating mutations in cells from patients with mastocytosis, we hypothesized that these mutations would also enhance chemotaxis. Indeed, mast cell precursors with activating mutations in Kit migrated towards SCF to a greater degree, offering one explaination for the increase in mast cells observed in tissues of patients with mastocytosis. Mast cells produce substances with anti-inflammatory properties in addition to their capacity to release proinflammatory mediators. To further probe the anti-inflammatory aspect of mast-cell function, we investigated the ability of human mast cells to produce interleukin(IL)-1 receptor antagonist (IL-1ra). Using a variety of methods, IL-1ra message and protein were found to be constitutively expressed in human mast cells. Upon stimulation through FceRI, IL-1ra protein was secreted from cultured mast cells and isolated human lung mast cells. In lavage fluids obtained from allergic asthmatic subjects, IL-1ra production increased after specific antigen challenge, with the 17-kD isoform of IL-1ra predominating. Thus, human mast cells release IL-1ra after activation, which may contribute to a local inhibition of IL-1-dependent effects on inflammation in the lung.